This project is designed to explore a new concept - that the regulation of anterior pituitary hormone secretion may involve not only quantitative control of secretion rates, but also influences upon the quality (biological activity) of some or all of these hormones. In the case of one of the anterior pituitary hormones, follicle-stimulating hormone, the ratio of biological to immunological activity has been found to change as a consequence of steroid hormone feedback. This change in the biological quality of FSH correlates with the overall ability of the hormone to survive in the circulation. Studies of metabolic clearance patterns show that prolonged circulatory survival of the endogenous circulating FSH in androgen-treated rats is attributable to a shift in the components of multiexponential decay curves (providing a metabolic "finger print" of the composition of a heterogeneous mixture of variously bioactive molecules). Similar studies will be done to see whether compositional changes can be detected in circulating or stored forms of other anterior pituitary hormones (luteinizing hormone, prolactin, thyrotrophin and somatotrophin) following various physiological manipulations designed to alter rates of secretion of these protein molecules. Control studies with injected hormone will be done to determine whether any changes in metabolic clearance patterns could be due to peripheral metabolic effects. If these studies provide evidence that any such manipulation does have a qualitative influence on the biosynthesis of a particular hormone, studies will be done to a) determine optimum conditions for demonstrating the resultant chemical pleomorphism, and b) define the nature of the chemical change.